Checkpoint Kinase MEC1 (ATR) Structure Reveals Activation Mechanism.

abstract：:Activating mutations in the EGF receptor (EGFR) are associated with clinical responsiveness to EGFR tyrosine kinase inhibitors (TKI), such as erlotinib and gefitinib. However, resistance eventually arises, often due to a second EGFR mutation, most commonly T790M. Through a genome-wide siRNA screen in a human lung canc...

journal_title：Cancer discovery

authors： de Bruin EC,Cowell C,Warne PH,Jiang M,Saunders RE,Melnick MA,Gettinger S,Walther Z,Wurtz A,Heynen GJ,Heideman DA,Gómez-Román J,García-Castaño A,Gong Y,Ladanyi M,Varmus H,Bernards R,Smit EF,Politi K,Downward J

更新日期：2014-05-01 00:00:00

abstract：:CD14+CD16-HLA-DRhi monocyte frequency was linked to response to anti-PD-1 in patients with melanoma. ...

journal_title：Cancer discovery

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更新日期：2018-03-01 00:00:00

abstract：:The FDA authorized 23andMe to market the first direct-to-consumer test to check for three BRCA1/2 mutations associated with a higher risk of developing breast, ovarian, and prostate cancers. The mutations are most commonly found in about 2% of women of Ashkenazi Jewish descent. ...

journal_title：Cancer discovery

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更新日期：2018-05-01 00:00:00

abstract：:A new compound with anti-leukemia activity perturbs gene transcription by modulating super-enhancer activity. ...

journal_title：Cancer discovery

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更新日期：2015-12-01 00:00:00

abstract：:Results from a randomized phase II study indicate that adding the experimental antibody IMAB362, which targets the tight junction protein claudin18.2, to standard chemotherapy is more effective than chemotherapy alone in previously untreated patients with advanced gastric cancer. IMAB362 extended progression-free and ...

journal_title：Cancer discovery

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更新日期：2016-08-01 00:00:00

abstract：:Asparagine promotes the survival of cancer cells in response to glutamine withdrawal. ...

journal_title：Cancer discovery

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更新日期：2014-11-01 00:00:00

abstract：:Somatic ERBB3 hot-spot mutations promote oncogenic signaling in a subset of human tumors. ...

journal_title：Cancer discovery

authors：

更新日期：2013-07-01 00:00:00

abstract：:Unconventional T-lymphocyte populations are emerging as important regulators of tumor immunity. Despite this, the role of TCRαβ+CD4-CD8-NK1.1- innate αβ T cells (iαβT) in pancreatic ductal adenocarcinoma (PDA) has not been explored. We found that iαβTs represent ∼10% of T lymphocytes infiltrating PDA in mice and human...

journal_title：Cancer discovery

authors： Hundeyin M,Kurz E,Mishra A,Rossi JAK,Liudahl SM,Leis KR,Mehrotra H,Kim M,Torres LE,Ogunsakin A,Link J,Sears RC,Sivagnanam S,Goecks J,Islam KMS,Dolgalev I,Savadkar S,Wang W,Aykut B,Leinwand J,Diskin B,Adam S,Is

更新日期：2019-09-01 00:00:00

abstract：:HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability and activity of the novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or HER2-mutant so...

journal_title：Cancer discovery

authors： Tsurutani J,Iwata H,Krop I,Jänne PA,Doi T,Takahashi S,Park H,Redfern C,Tamura K,Wise-Draper TM,Saito K,Sugihara M,Singh J,Jikoh T,Gallant G,Li BT

更新日期：2020-05-01 00:00:00

abstract：:The FDA approved atezolizumab to treat advanced bladder cancer when cisplatin chemotherapy is contraindicated. The approval offers a potentially more effective alternative to carboplatin-based chemotherapy for frail, elderly patients. ...

journal_title：Cancer discovery

authors：

更新日期：2017-06-01 00:00:00

abstract：:A phase II study indicates that sacituzumab govitecan (IMMU-132), a Trop-2-specific antibody linked to the irinotecan metabolite SN-38, prolongs the progression-free survival of patients with advanced triple-negative breast cancer. IMMU-132 is well tolerated, causing fewer and more manageable side effects than irinote...

journal_title：Cancer discovery

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更新日期：2016-01-01 00:00:00

abstract：:Although BRAF-MEK inhibition can enhance the immune recognition of melanoma cells, the mechanisms that underlie this remain poorly defined. In this issue of Cancer Discovery, Erkes and colleagues present new data showing that BRAF-MEK inhibition activates pyroptosis in melanoma cells through gasdermin E cleavage, lead...

journal_title：Cancer discovery

authors： Smalley KSM

更新日期：2020-02-01 00:00:00

abstract：UNLABELLED:CD96 has recently been shown as a negative regulator of mouse natural killer (NK)-cell activity, with Cd96(-/-)mice displaying hyperresponsive NK cells upon immune challenge. In this study, we have demonstrated that blocking CD96 with a monoclonal antibody inhibited experimental metastases in three different...

journal_title：Cancer discovery

authors： Blake SJ,Stannard K,Liu J,Allen S,Yong MC,Mittal D,Aguilera AR,Miles JJ,Lutzky VP,de Andrade LF,Martinet L,Colonna M,Takeda K,Kühnel F,Gurlevik E,Bernhardt G,Teng MW,Smyth MJ

更新日期：2016-04-01 00:00:00

abstract：:Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis, and new strategies for prevention and treatment are urgently needed. We previously reported that histone H4 acetylation is elevated in pancreatic acinar cells harboring Kras mutations prior to the appearance of premalignant lesions. Because acetyl-CoA abunda...

journal_title：Cancer discovery

authors： Carrer A,Trefely S,Zhao S,Campbell SL,Norgard RJ,Schultz KC,Sidoli S,Parris JLD,Affronti HC,Sivanand S,Egolf S,Sela Y,Trizzino M,Gardini A,Garcia BA,Snyder NW,Stanger BZ,Wellen KE

更新日期：2019-03-01 00:00:00

abstract：:Translational data on chimeric antigen receptor (CAR) T-cell trials indicate that the presence of naïve T cells in the premanufacture product is important to clinical response and persistence. In anticipation of developing CAR trials for other tumors, we investigated the T-cell distribution from children with solid tu...

journal_title：Cancer discovery

authors： Das RK,Vernau L,Grupp SA,Barrett DM

更新日期：2019-04-01 00:00:00

abstract：:A multidisciplinary panel of experts has issued guidelines that consolidate current evidence on testing for molecular biomarkers in colorectal cancer. The guidelines aim to standardize molecular testing for patients with colorectal cancer and help clinicians identify patients most likely to benefit from targeted treat...

journal_title：Cancer discovery

authors：

更新日期：2017-04-01 00:00:00

abstract：:A new study by Juergens and colleagues provides the first successful example of a combined epigenetic therapy capable of achieving results similar to those of conventional chemotherapy in refractory metastatic non-small cell lung cancer. Furthermore, the authors describe interesting blood-based DNA methylation biomark...

journal_title：Cancer discovery

authors： Rodríguez-Paredes M,Esteller M

更新日期：2011-12-01 00:00:00

abstract：:Even in diffuse large B-cell lymphoma (DLBCL), a cancer of professional antigen-presenting cells, response rates to immune checkpoint blockade therapy have been limited. One reason for DLBCL immune evasion is epigenetic repression instead of activation of the antigen-presenting MHC-a dissection of mechanisms underlyin...

journal_title：Cancer discovery

authors： Velcheti V,Wong KK,Saunthararajah Y

更新日期：2019-04-01 00:00:00

abstract：:Researchers have used mass spectrometry to conduct proteomic analyses of 77 genomically characterized breast tumors. Through this approach, they've uncovered functional consequences of somatic mutations. For instance, EGFR overexpression in basal-like breast cancer is potentially driven by the loss of two genes, SKP1 ...

journal_title：Cancer discovery

authors：

更新日期：2016-08-01 00:00:00

abstract：:Researchers have developed an antibody-drug conjugate with the potential to treat neuroblastoma. The agent targets ALK, which is found on neuroblastoma cells but not healthy cells, delivering a drug that causes DNA cross-links. Researchers have found that the antibody-drug conjugate kills ALK-expressing cells in vitro...

journal_title：Cancer discovery

authors：

更新日期：2019-06-01 00:00:00

abstract：: BRAF fusions and mutations are the most frequent genetic alterations in pediatric low-grade gliomas. The work from Wang and colleagues identifies an acquired secondary BRAF mutation that confers resistance to pharmacologic BRAF inhibition in a BRAFV600E glioma. The authors demonstrate that the mu...

journal_title：Cancer discovery

authors： Romano G,Kwong LN

更新日期：2018-09-01 00:00:00

abstract：:Pancreatic ductal adenocarcinoma (PDAC) is poorly responsive to therapies and histologically contains a paucity of neoplastic cells embedded within a dense desmoplastic stroma. Within the stroma, cancer-associated fibroblasts (CAF) secrete tropic factors and extracellular matrix components, and have been implicated in...

journal_title：Cancer discovery

authors： Biffi G,Oni TE,Spielman B,Hao Y,Elyada E,Park Y,Preall J,Tuveson DA

更新日期：2019-02-01 00:00:00

abstract：:An international team of researchers has uncovered multiple new germline mutations that may influence the development of sarcomas. Notably, they found that variants in several DNA damage sensing and repair genes contribute greatly to sarcoma risk, including BRCA2, ATM, ATR, and ERCC2. ...

journal_title：Cancer discovery

authors：

更新日期：2016-10-01 00:00:00

abstract：:LKB1 inactivation generates a redox imbalance that promotes ADC-to-SCC transdifferentiation in NSCLC. ...

journal_title：Cancer discovery

authors：

更新日期：2015-07-01 00:00:00

abstract：:Activation of AKT signaling by PTEN loss or PIK3CA mutations occurs frequently in human cancers, but targeting AKT has been difficult due to the mechanism-based toxicities of inhibitors that target the inactive conformation of AKT. Ipatasertib (GDC-0068) is a novel selective ATP-competitive small-molecule inhibitor of...

journal_title：Cancer discovery

authors： Saura C,Roda D,Roselló S,Oliveira M,Macarulla T,Pérez-Fidalgo JA,Morales-Barrera R,Sanchis-García JM,Musib L,Budha N,Zhu J,Nannini M,Chan WY,Sanabria Bohórquez SM,Meng RD,Lin K,Yan Y,Patel P,Baselga J,Tabernero J,

更新日期：2017-01-01 00:00:00

abstract：:CD30-directed CAR T cells were safe and produced a 62% overall response rate in Hodgkin lymphoma. ...

journal_title：Cancer discovery

authors：

更新日期：2020-09-01 00:00:00

abstract：:A phase II study of the PARP inhibitor olaparib (AstraZeneca) for cancer patients with inherited BRCA1 and BRCA2 gene mutations confirmed earlier results showing clinical benefit for advanced breast and ovarian cancers, and demonstrated evidence of effectiveness against pancreatic and prostate cancers. ...

journal_title：Cancer discovery

authors：

更新日期：2013-07-01 00:00:00

abstract：:Inosine produced by the gut microbe Bifidobacterium pseudolongum enhanced anti-CTLA4's efficacy. ...

journal_title：Cancer discovery

authors：

更新日期：2020-10-01 00:00:00

abstract：:Recent results suggest that tucatinib, when combined with trastuzumab and capecitabine, is effective in patients with locally advanced inoperable or metastatic HER2-positive breast cancer who have received prior therapies: In a phase II trial, the drug extended overall survival and progression-free survival compared w...

journal_title：Cancer discovery

authors：

更新日期：2020-01-01 00:00:00

abstract：:By law, the U.S. Food and Drug Administration has the authority, through its Center for Tobacco Products, to regulate the manufacture, marketing, and distribution of tobacco products. Its director, Mitchell Zeller, JD, talks about how the center, though its research, public education, and enforcement activities, aims ...

journal_title：Cancer discovery

authors： Zeller M,Rose S

更新日期：2014-01-01 00:00:00